The proposed Autoimmunity Prevention Center combines the efforts of investigators with faculty appointments at the University of Colorado Health Sciences Center (UCHSC), Denver Colorado and the Virginia Mason Center (University of Washington) in Seattle Washington. Affiliated institutions at the UCHSC include the Barbara Davis Center for Childhood Virginia Mason Center and the Barbara Davis Center/UCHSC have a long history of collaborative efforts and complementary expertise in the field of immunology of autoimmunity. In particular the laboratories of Brian Kotzin and reagents as part of the Immune Tolerance Network. T cell clones derived at the Barbara Davis Center are being utilized by Dr. Nepom to create tetramers to identify diabetogenic T cells. Drs. Eisenbarth and Greenbaum are co-investigators on an NIH study of diabetes protective HLA alleles. A joint clinical trial of mycophenolate mofetil and IL2 receptor antibodies for new onset diabetes is about to commence at the Virginia Mason Center and the Barbara Davis Center. We are committed to a collaborative effort between the two institutions, with Dr. Eisenbarth going on sabbatical to work in the laboratories of Kwok and Nepom for 6 months beginning in July of 2001. In addition, we welcome the opportunity to extend collaborative efforts to a prevention Center Network. Faculty for the Prevention Center have been recruited from the Departments of Immunology, Pediatrics, Medicine, and Preventive Medicine, Epidemiology, and the Human Medical Genetics Program. Within the Departments of Pediatrics and Medicine, subspecialties include endocrinology, rheumatology, clinical immunology, nephrology, pulmonary, and gastroenterology. There are unique resources for clinical investigation and strong basic science faculty and in many instances a track record for combining basic and clinical investigation. For the current proposal, the DAISY prospective study of children developing diabetes provides an essential resource and paradigm for the study of human autoimmunity in families and the general population and we are looking forward to joint studies of celiac disease, rheumatoid arthritis, polychondritis, and type 1 diabetes. Three Projects are proposed. Project 1 Quantitate and Characterize T cells of Type 1 diabetes; Project 2 Initiate studies of rheumatoid arthritis modeled on studies such as DAISY; Project 3 Analyze the development of celiac disease autoimmunity of infants followed from birth. Two Pilot studies are also proposed, one evaluating polychondritis and the other evaluating in basic animal models the importance of specific signaling pathways (CD32 and phosphatidylserine receptor) to maintenance of tolerance and development of autoimmunity.